1. Field of the Invention
This invention relates to a novel fibrinogen and fibronectin binding protein from group A streptococci, and the DNA encoding the protein. The protein and its DNA are useful in the preparation of compositions for the diagnosis, treatment, and prevention of streptococcal infection.
2. Description of the Related Art
Among surface proteins of gram-positive bacteria, the fibronectin-binding (Fn-binding) proteins are responsible for adhesion to host epithelial cells (11, 12). Accordingly, Fn-binding proteins may provide the bacterial cell with the means to initiate the infection process (11, 12, 13, 14). Fn-binding proteins have been identified in Staphylococcus aureus (3, 11, 16), class I (SOF) S. pyogenes (10, 12, 15) and Streptococcus dysgalactiae (6, 14). Sequence analysis of these proteins revealed that they are large cell surface proteins, with a predicted size range of 73-122 kDa. The domain architecture of these molecules is similar: a divergent N-terminal portion which constitutes up to 80% of their sequence, followed by three to five homologous tandem Fn-binding repeats of from 32 to 43 residues each (3, 6, 12, 15, 16). In at least two cases, protein F from S. pyogenes class I and FnBPB from S. aureus, a region of approximately 50 residues N terminal to the tandem repeats has also been implicated as essential for maximal Fn-binding activity (3, 15). A putative cell wall-spanning segment is located C terminally to the repeats, followed by a typical gram-positive cell attachment motif.
Group A Streptococci (Streptococcus pyogenes) is the etiologic agent for different suppurative infections (e.g., pharyngitis, impetigo, and necrotizing fasciitis) as well as systemic diseases (e.g., scarlet fever, toxic shock-like syndrome), some of which may lead to serious sequelae, such as rheumatic fever and glomerulonephritis. The ability to bind fibronectin has proven to be one of the mechanisms Streptococcus pyogenes use for attachment to host cells (5, 8, 10). Since this glycoprotein is present in body fluids, extracellular matrices, and on the surface of mammalian cells, the identification and characterization of new fibronectin-binding proteins is likely to have pathogenic significance.